Thyroidhormoneexertsitscardiacactionsbytwopaths:genomicandnongenomic.Thegenomicrouteinvolvesinteractionofthyroxine(T3)withnuclearreceptorsthatregulatethetranscriptionofT3-responsivegenes.Inhyperthyroidism,messengermRNAforcardiacmyocyteproteinsinvolvedinregulatingintracellular[Ca++](e.g.,sarcoplasmicendoplasmicreticulumcalcium-ATPase[SERCA],ryanodinechannel)isincreased,asareamountsofcontractileproteins(e.g.,myosinheavychain,actin,troponinI).Consequently,theratesofcontractionandrelaxationincreaseasATPhydrolysisandO2consumptionincrease.Inthehyperthyroidstate,theuseofATPislessefficient,andthefractionallossofheatisgreater.Ifuntreated,severehyperthyroidismcanresultinheartfailure.
Cardiacactivityisdepressedinpatientswithinadequatethyroidfunction(hypothyroidism).Theconverseistrueinpatientswithoveractivethyroidglands(hyperthyroidism).Characteristically,patientswithhyperthyroidismexhibittachycardia,highcardiacoutput,andarrhythmiassuchasatrialfibrillation.Insuchpatients,sympatheticneuralactivitymaybeincreased,orthesensitivityofthehearttosuchactivitymaybeenhanced.Studieshaveshownthatthyroidhormoneincreasesthedensityofβ-adrenergicreceptorsincardiactissue(seealso ).Inexperimentalanimals,thecardiovascularmanifestationsofhyperthyroidismmaybesimulatedbytheadministrationofexcessthyroxine.
increases the body’s metabolic rate, which in turn results in arteriolar vasodilation. The consequent reduction in total peripheral resistance increases cardiac output, as explained in
Insulin has a positive inotropic effect on the heart. The effect of insulin is evident even when hypoglycemia is prevented by glucose infusions and when β-adrenergic receptors are
CHAPTER 18 Regulation of the Heart and Vasculature blocked. Indeed, the positive inotropic effect of insulin is potentiated by β-adrenergic receptor antagonists. The enhanced contractility cannot be explained satisfactorily by the concomitant augmentation of glucose transport into myocardial cells.
Glucagon has potent positive inotropic and chronotropic effects on the heart. This endogenous hormone is probably not important in normal regulation of the cardiovascular system, but it has been used clinically to enhance cardiac performance. The effects of glucagon on the heart and certain metabolic effects are similar to those of catecholamines. Both glucagon and catecholamines activate adenylate cyclase to increase myocardial levels of cAMP. The catecholamines activate adenylate cyclase by interacting with β-adrenergic receptors, but glucagon activates this enzyme by a different mechanism. Nevertheless, the rise in cAMP increases influx of Ca++ through calcium channels in the sarcolemma and facilitates release and reuptake of Ca++ by the sarcoplasmic reticulum, just as catecholamines do.
The cardiovascular derangements in hypopituitarism are related principally to the associated deficiencies in adrenocortical and thyroid function. Growth hormone affects the myocardium, at least in combination with thyroxine. In hypophysectomized animals, growth hormone alone has little effect on the depressed heart, whereas thyroxine by itself restores adequate cardiac performance under basal conditions. However, when blood volume or peripheral resistance is increased, thyroxine alone does not restore adequate cardiac function, but the combination of growth hormone and thyroxine reestablishes normal cardiac performance. In certain animal models of heart failure, administration of growth hormone alone increases cardiac output and myocardial contractility.